Motivation

• We need to be able to evaluate and compare existing and new influenza vaccines.
• Immunogenicity is often a good correlate for protection. For flu specifically, HA antibodies.
• To assess broad protection, we need to quantify antibody responses to a panel of flu strains.

Quantifying vaccine responses

Quantifying vaccine responses

Quantifying vaccine responses

Comparing vaccine responses

A new method to quantify/compare vaccine responses

• Organize strains by antigenic distance
• Fit a model to more robustly estimate magnitude/breadth/strength

Strain distance

Quantifying vaccine responses

Comparing vaccine responses

Testing our method

We sampled from the panel of heterologous strains from UGAFluVac to mimic different labs

Testing our method - the results

Part 1 Summary & Discussion

• Our proposed new method seems to be more robust and suitable to quantify and compare vaccine responses.
• We would like to compare the method across actual separate studies.
• Include ‘future’ strains into analysis.
• Compare different distance measures.
• Explore models beyond linear.

Motivation

• Pre-clinical/animal studies are an important part of the vaccine development pathway.
• Results in animals inform choices for subsequent human studies.
• We need to be able to properly assess influenza vaccine efficacy in animals.

Motivation

• For both humans and animals, vaccine protection from infection/disease is the gold standard.
• Immunogenicity is often a good correlate of protection (CoP). For flu specifically, HA antibodies.
• CoP in humans are only somewhat understood. They are even less studied in animals.

CoP in adults

Hobson et al.: https://pmc.ncbi.nlm.nih.gov/articles/PMC2130285/

CoP in children

Ng et al.: https://pubmed.ncbi.nlm.nih.gov/23908481/

CoP meta-analysis

Coudeville et al.: https://pubmed.ncbi.nlm.nih.gov/20210985/

CoP in animals

• What’s the relation between antibody titers and outcomes?
• Does a 1:40 titer correspond to 50% protection in mice, ferrets, guinea pigs, etc.?

CoP in mice

Jacobsen et al.: https://pubmed.ncbi.nlm.nih.gov/28928215/

CoP in ferrets

Wong et al.: https://pubmed.ncbi.nlm.nih.gov/28303960/

Part 2 Summary & Discussion

• Not much known about CoP in animals.
• We could model the mapping from CoP to outcomes with the right kind of data:
  • CoP data: antibody (and/or other immunological) measurements in non-naive animals prior to challenge
  • Outcome data: Infection, weight loss, symptoms, viral load, etc.
• Broader: Relation between CoP in animals to CoP in humans?